The LINC complex and human disease.

@article{Meinke2011TheLC,
  title={The LINC complex and human disease.},
  author={Peter Meinke and Thuy Duong Nguyen and Manfred S. Wehnert},
  journal={Biochemical Society transactions},
  year={2011},
  volume={39 6},
  pages={
          1693-7
        }
}
The LINC (linker of nucleoskeleton and cytoskeleton) complex is a proposed mechanical link tethering the nucleo- and cyto-skeleton via the NE (nuclear envelope). The LINC components emerin, lamin A/C, SUN1, SUN2, nesprin-1 and nesprin-2 interact with each other at the NE and also with other binding partners including actin filaments and B-type lamins. Besides the mechanostructural functions, the LINC complex is also involved in signalling pathways and gene regulation. Emerin was the first LINC… 
View on PubMed
biochemsoctrans.org
80 Citations
Highly Influential Citations
4
Background Citations
38

Figures and Tables from this paper

80 Citations

Citation Type

Citation Type

LINCing Defective Nuclear-Cytoskeletal Coupling and DYT1 Dystonia
Mechanical forces generated by nuclear-cytoskeletal coupling through the linker of nucleoskeleton and cytoskeleton (LINC) complex, an evolutionarily conserved molecular bridge in the nuclear envelope…
Nesprin-1/2: roles in nuclear envelope organisation, myogenesis and muscle disease.
TLDR
Recent advances in the understanding of the functions of nesprin-1/2 in the LINC complex are reviewed and mechanistic insights into how mutations in nes Prins lead to nesPrin-related muscle diseases, in particular DCM and EDMD are reviewed.
Nucleoskeleton dynamics and functions in health and disease
TLDR
This review will focus principally on the subcomplex of the cytoskeleton associated with the nucleus, often referred to as the nucleoskeleton, but in the context of its extensive interconnectivity with the rest of the nucleus and with cytoplasmic filament systems all the way to the exoskeleton.
A Glance at the Nuclear Envelope Spectrin Repeat Protein 3
TLDR
This review will focus on nesprin-3, examining it from a genetic, structural, and functional perspective, and address the limitations of existing research and the future perspectives for the study of nes PRIN-3.
A molecular model for LINC complex regulation: activation of SUN2 for KASH binding
TLDR
A computational approach was used to model a fragment of SUN2 containing CC1, CC2, and the SUN domain and showed that the interplay between CC1 and CC2 may be sufficient for the release of CC2-SUN2 from its autoinhibited state.
A molecular mechanism for LINC complex branching by structurally diverse SUN-KASH 6:6 assemblies
TLDR
Evidence is provided that SUN-KASH is a constitutive 6:6 complex in which two constituent 3:3 complexes interact head-to-head, enabling the coordinated transduction of large forces across the nuclear envelope.
The diverse functional LINCs of the nuclear envelope to the cytoskeleton and chromatin
TLDR
The function of SUN and KASH domain proteins in various unicellular and multicellular species and the role of LINC complexes in nuclear anchorage and migration as well as in genome organization are reviewed.
SUN/KASH interactions facilitate force transmission across the nuclear envelope
TLDR
In vivo functions of conserved interfaces revealed by crystal structures are tested for conserved aromatic residues at the -7 position of the C-termini of KASH proteins and conserved disulfide bonds in LINC complexes, which play important roles in force transmission across the nuclear envelope.
A molecular mechanism for LINC complex branching by structurally diverse SUN-KASH 6:6 assemblies
The LINC complex mechanically couples cytoskeletal and nuclear components across the nuclear envelope to fulfil a myriad of cellular functions, including nuclear shape and positioning, hearing and…
Global loss of a nuclear lamina component, lamin A/C, and LINC complex components SUN1, SUN2, and nesprin-2 in breast cancer
TLDR
Using immunohistology, it is found that a nuclear lamina component, lamin A/C and all of the investigated LINC complex components, SUN1, SUN2, and nesprin‐2, were downregulated in human breast cancer tissues.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 41 REFERENCES
Dynamics and molecular interactions of linker of nucleoskeleton and cytoskeleton (LINC) complex proteins
TLDR
The data support a model in which A-type lamins and Sun2 anchor nesprin-2 in the outer nuclear membrane, whereas emerin, Sun1 and actin are dispensable for this anchoring.
Mammalian SUN Protein Interaction Networks at the Inner Nuclear Membrane and Their Role in Laminopathy Disease Processes*
TLDR
Emerin and short nesprin-2 isoforms are identified as novel nucleoplasmic binding partners of SUN1/2 and proposed that these different perturbations in lamin A-SUN protein interactions may underlie the opposing effects of EDMD and HGPS mutations on nuclear and cellular mechanics.
Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity.
TLDR
Data suggest that EDMD may be caused, in part, by uncoupling of the nucleoskeleton and cytoskeleton because of perturbed nesprin/emerin/lamin interactions.
Altered mechanical properties of the nucleus in disease.
Nesprin-2 giant safeguards nuclear envelope architecture in LMNA S143F progeria cells.
TLDR
It is demonstrated here that patient dermal fibroblast cells have dysmorphic nuclei containing numerous blebs and lobulations, which progressively accumulate as cells age in culture, and a direct involvement of the nesprin-2 giant as a structural reinforcer at the NE is implicate.
Coupling of the nucleus and cytoplasm
TLDR
Data from this study support a model in which Sun proteins tether nesprins in the ONM via interactions spanning the PNS, and form a complex that links the nucleoskeleton and cytoskeleton (the LINC complex).
The role of nesprins as multifunctional organizers in the nucleus and the cytoskeleton.
Nesprins (nuclear envelope spectrin repeat proteins), also known as SYNE (synaptic nuclear envelope protein), MYNE (myocyte nuclear envelope protein), ENAPTIN and NUANCE, are proteins that are…
Nuclear envelope alterations in fibroblasts from patients with muscular dystrophy, cardiomyopathy, and partial lipodystrophy carrying lamin A/C gene mutations
TLDR
Results confirm that mutations in lamins A and C may lead to a weakening of a structural support network in the nuclear envelope in fibroblasts and that nuclear architecture changes depend upon the location of the mutation in different domains of lamin A/C.
Direct interaction between emerin and lamin A.
TLDR
Direct interaction between recombinant emerin and lamin A molecules is demonstrated using biomolecular interaction analysis (BIA) and monoclonal antibodies.
Linear Arrays of Nuclear Envelope Proteins Harness Retrograde Actin Flow for Nuclear Movement
TLDR
The coupling of actin cables to the nuclear membrane for nuclear movement via specific membrane proteins indicates that, like plasma membrane integrins, nuclear membrane proteins assemble into actin-dependent arrays for force transduction.
...
1
2
3
4
5
...